Mechanistic insight into angiotensin II type 2 receptor (AT2R) nephroprotective effect during renal ischemia/reperfusion

RIVABELLA MAKNIS T; FUSSI MF; PARIANI A; HUHN V; FAVRE C; MOLINAS SM; LAROCCA MC

Congreso; PANAM2023 Physiologycal Sciences; 2023

Mechanistic insight into angiotensin II type 2 receptor (AT2R) nephroprotective effect during renal ischemia/reperfusionRivabella Maknis T1, Fussi MF1, Pariani AP1, Huhn V1, Favre C1, Molinas SM1, Larocca MC1.1Instituto de Fisiología Experimental (IFISE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (FBIOyF), Universidad Nacional de Rosario (UNR), Argentina.IntroductionAT2R agonist C21 elicits nephroprotective effects in ischemia/reperfusion (IR)-induced acute kidney injury (AKI) by preventing tubular cell damage. IR-induced AKI is associated with tubular cell deciliation. Primary cilia are sensory organelles, whose stability depends on α-tubulin acetylation. Extracellular signal-regulated kinases (ERK) activate α-tubulin deacetylase HDAC6.ObjectiveTo get mechanistic insight for C21 nephroprotective effect during IR.MethodsMale Wistar rats were pretreated 24h with C21 0,3 mg/kg/day and subjected to unilateral renal IR (n=3-5 rats per group; Institutional Animal Care and Use Committee-FBIOyF Resolution #023-2020). C21 effect was also assessed using a serum/ATP depletion model of IR in MDCK cells (n=3-4 independent experiments). C21 or MEK1/2 inhibitors (PD98059 5μM or U0126 10μM) were added to the media 24h before IR. Cell ciliation, relative cilia levels of acetylated-α-tubulin (c-Ac-αtub) and ERK1/2 localization were analyzed by immunofluorescence microscopy, activated ERK (pERK) by immunoblotting and cell viability by Trypan blue exclusion test. For cilia length, results are expressed as media±SEM. ANOVA/Holm-Sidak-test, Kruskal-Wallis/Dunn’s-test or t-test were applied. *p